Bruton's tyrosine kinase (hereinafter, abbreviated as “Btk”) belongs to the Tec family of kinases, which are non-receptor tyrosine kinases, and is selectively expressed in the B cell and myelocyte lines. Btk plays an important role in signal transduction in B cells and is a factor that contributes to the survival, differentiation, proliferation, and activation of B cells. Signaling in B cells via the B cell antigen receptor (BCR) induces a broad range of biological responses, and abnormal signal transduction here causes abnormal B cell activation and the formation of pathogenic autoantibodies. Btk is believed to form a link in the BCR-mediated signal transduction pathways into B cells. In recent years, clinical tests of a Btk inhibitor directed to a variety of B-cell non-Hodgkin's lymphomas have been conducted, and for example, it has been reported that Ibrutinib shows effectiveness in patients with diffuse large B-cell lymphoma (hereinafter, may be abbreviated as DLBCL) (see 54th American society of hematology (ASH), session: 623, program No.: 686, “The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study”, abstract, 2012).
DLBCL is roughly classified into two kinds of activated B-cell like (ABC) and germinal center B-cell like (GCB) depending on a difference in the gene expression profile thereof, and it is known that the former (hereinafter, may be abbreviated as ABC-DLBCL) is of poor prognosis as compared with the latter (hereinafter, may be abbreviated as GCB-DLBCL) (see Nature, Vol. 403, pages 503-511, 2000). Even when treatment is conducted which uses standard treatment methods of B-cell lymphoma, such as radiation, anticancer agents, biological preparations such as Rituxan, or hematopoietic stem cell transplantation, particularly patients with ABC-DLBCL show treatment resistance (refractory) or may repeatedly show recurrence, and therefore, a drug which can attain complete remission of ABC-DLBCL has been desired.
Further, in ABC-DLBCL, mutation is also seen in genes related to NFκ B-cell signaling pathway, such as CD79B and MYD88. CD79B is a membrane protein which forms a protein complex of a B-cell receptor together with CD79A and antigen-specific immunoglobulin. It is known that when there is CD79B mutation, NFκB signaling is constantly activated; however, among ABC-DLBCL patients, frequency thereof is merely about 20 to 30%. Therefore, an agent which can show effectiveness on ABC-DLBCL treatment irrespective of the presence or absence of CD79B mutation has been also desired.
On the other hand, it has been reported that ONO-4059 being the same Btk inhibitor is subjected to a clinical trial in a variety of subtypes of B-cell non-Hodgkin's lymphomas including mantle cell lymphoma and ABC-DLBCL (see 55th American society of hematology (ASH), session: 624, program No.: 4397, “A Phase I Study Of The Oral Btk Inhibitor ONO-4059 In Patients With Relapsed/Refractory B-Cell Lymphoma”, abstract, 2013, American Society of Clinical Oncology (ASCO), annual meeting 2014, program No.: 8553, “The Bruton's Tyrosine Kinase (BTK) Inhibitor ONO-4059: Promising Single Agent Activity in Patients with Relapsed and Refractory Non-GCB-DLBCL”, abstract). It has been disclosed that the present compound is effective in DLBCL treatment (see WO 2011/152351 and WO 2013/081016), but both the prior art documents do not describe or suggest that the present compound shows prominent effect on which subtype of B-cell non-Hodgkin's lymphoma as compared with other agents.